Synthesis applications of aza-cope rearrangements

SYNTHESIS APPLICATIONS OF AZA-COPE REARRANGEMENTS A STEREOSELECTIVE SYNTHESIS OF 9a-ARYLHYDROLILOLIDINES [AND A NEW APPROACH TO THE SYNTHESIS OF ASPIDOSPERMA] ALKALOIDS LARRYE. OVERMAN* and Department

of Chemistry,

University

MICHAEL SWORIN

of California,

Irvine, CA 92717, U.S.A.

and LAWRENCE S. BASSand JONCWRDY Department

of Chemistry, Cornell University,

Ithaca, NY 14853. U.S.A.

(Received in USA May 5 1981) Abstract-A “Mannichdirected” 2-azonia-[3,3]-sigmatropic rearrangement is the key step in a new, completely stereoselective, method for preparing 9aarylhydrolilolidines. Specifically, &fused bicyclic aminoalcohols 24 upon treatment with formaldehyde and acid afford hydrolilolidines 25 in a single step and in excellent yield. The complete stereoselectivity of this “ring-enlarging pyrrolidine annulation” reaction follows stereorationally from the Irons-relationship of vinyl and amine functions in the bicyclic precursor 24 (eqn 6).

The cationic azaCope rearrangement (2-azonia-[3,3]sigmatropic rearrangement, eqn 1) was first described by Geissman’** in 1950.This reversible C-C bond-forming reorganization occurs under remarkably mild conditions, typically at or near room temperature and, thus, 100-200“ below that of the corresponding Cope rearrangements.‘** Since, in our view, the major impediment to general use of

to direct the course of the aza-Cope rearrangement by capturing the rearranged sigmatropic isomer in an intramolecular Mannich fashion (eqh 3). When the starting

(1)

iminium

I

ion was formed intramolecularly, this reaction was extended to achieve a one-step indolizidine annulation (4-S), which was the key step in our5 recent total synthesis of dl-perhydrogephyrotoxin (a).”

2

this reaction in synthesis was its reversibility, recent studies in our laboratory-’ have had as their objective the development of general methods for “directing” this rearrangement so that it would be irreversible (l-+2) in the desired direction. Our original report3 described the reaction of salts of 2-alkoxy-3-butenamines with a variety of aldehydes to produce 3-acylpyrrolidines in a single step, and in excellent yield (eqn 2). This pyrrolidine synthesis exploited the stability of a properly placed 0 substituent

4

3

H .’ H HN

-‘:*

k HO

6

5 TET Vol. 37.No. 2&L

We have also described’ a different and more unusual annulation sequence for the synthesis of cis-3a-aryloc4041

L. E. OVERMAN et at.

4042

tahydroindolones (7 + 8, R = CHPh,). This reaction provides a stereoselective entry to the widely occurrir$

completely stereoselective assembly of the tricyclic 9aarylhydrolilolidine’” ring system 12. Hydrolilolidines, which incorporate the synthetically demanding quaternary aryl functionality, have not to our knowledge been prepared previously.” ~ydroiilolidines of this type are key intermediates in a new approach to the Aspidosperma al~loids which is currently under investi~tion in our laboratory (eqn 5). The results described here document the general feasibility of this synthesis plan, and provide a further illustration of the utility of “dirrected” cationic aza-Cope rearrangements for the stereoselective synthesis of complex heterocyclic systems.

ff-0

1:

0 Clip0 R.S03H

-c

8

N

HA *’

6

7

..OH

Q

_
Crinina

ci~-3a-~yloc~hydroindole ring system, and was first utilized by us’ to achieve a formal total synthesis of the Amaryllidaceae alkaloid crinine. The formation of specifically the cis product from this “ring-enlarging pyrrolidine annulation” sequence follows sfe~e~~afi~~af~y from the tram orientation of the amine and vinyl groups in precursor 7. As a result of this tram relationship, the iminium ion 9 can undergo pericyclic rearrangement uia only a single “chair-type” transition-state to generate the truns,trans-I,S-azacyclononadiene 10 would yield cispresumed intermediate (eqn 41.’ Intramolecular Mannich ring closure of a~~ylononadiene 10 would yield ciso~tahydroindolone 8 stereospecifically.

7-&&&LA+-6 bn

’

R

f0

9

(41

In this paper we describe a further extension of the “ring-enlarging pyrrolidine annulation” sequence. In particular, we report the use of this reaction for the

Me0 Aspidospermo Al koloids (Vindoline) RESULTS

Since our primary interest in the Aspidosperma area are al~loids with unsaturation in the D ring, e.g. vindoline, we sought a general approach for preparing the bicyclic intermediate 11 (eqn 51, which either incorporated unsaturation in the piperidine ring of this intermediate or a heteroatom function R. A direct method for assembling systems of this latter type is summarized in Scheme I. Titanium tetrachloride promoted alkylation’2 of the thermodynamic trimethylsilyl enol ether 1313 of 2-ethylcyclopentanone with the diethy]‘” or dibenzyl” acetal of 3-ChloropropionaIdehyde 14 gave cyclopentanones 15 and 14 in 70% and 45% yields, respectively. The yield was somewhat lower with the benzyl acetal, since the dehenzylated product 17 was also produced under these conditions. Treatment of 16 with NaI in

-OSiMs3

w1 I

X-

I3 -I-

-1

;;Y+ I4

OBn

i-

15;

RsEt.

XcCl

16;

R=Bn,

X=CI

it,

RsH,

10;

R=Bn,

IS

X*Cl X* I

OBn-

220;

R’s ii,

R2= OBn

22b; RI= OBn, R2=H Scheme 1. Bn = CH?Ph.

Synthesis

applicationsof azaCope rearrangements

refluxing 2-butanone gave iodide 18, which reacted smoothly with methyl amine in the presence of anhydrous magnesium sulfate to afford the bicyclic enamines 19. Hydroboration of 19 by the procedure of Borowitz’6 gave a mixture of three of the four possible bicyclic alcohols in 75% yield from 16. These alcohols were partially separated by chromatography on silica gel and tentatively characterized by their 250MHz ‘H NMR spectra. However, they were more conveniently processed by DMSO-oxalyl chloride oxidation” and subsequent epimerization with sodium methoxide in refluxing methanol to give, after chromatographic separation, the two cis-bicyclic ketones 22a (S 3.36; dd, J = 4.1, 5.9 Hz) and 22b (S 3.51; dd, J = 4.4, 8.5 Hz) in yields of 31% and 29% from the alcohol mixture. An examination of molecular models leaves little doubt that the CL-fused isomer should be favored at equilibrium” for both benzyl diastereomers. Since one of our objectives was to ascertain what functionality could be tolerated in the piperidine ring during the “ring-enlarging pyrrolidine annulation” reaction, ketones 22a and 22b were not merged, but rather independently converted to the hydrolilolidine ring-system. This three step sequence is summarized for the a-benzyloxy series in Scheme 2. Reaction of 22a with 1-phenylvinyl lithium occurred to give a single alcohol 23a in 52% yield based on converted ketone. A consideration of molecular models leaves little doubt that the stereoselective addition must have occurred from the less-hindered convex a-face of ketone 22a (cf. the conformational drawing of 22a in Scheme 1). Phenyl chloroformate demethylation of 23~1gave aminoalcohol 24a in 55% yield. Pleasingly, when 24a was heated ’ in refluxing benzene for 4 hr with 2.5 equiv of paraformaldehyde and 0.9 equiv of d-IO-camphorsulfonic acid, hydrolilolidine 2Sa was obtained in 83% yield after chromatographic

4043

purification. A crystalline sample of Zsa, m.p. llS.S-116.5”, was obtained from pentane and showed characteristic signals in the ‘H NMR spectrum for an equatorial henzyloxy methine hydrogen at 6 3.37 (apparent t,J = 2.6 Hz) and a triplet at S 0.62 for the Me of the angular Et group. The strongly deshielded position of this Me signal is consistent only with a cis-l$diaxial orientation of the angular Et and Ph groups (Fig. I), while the axial orientation of the benzyloxy group can arise only if both ring-fusions are cis.19 The structural assignment for hydrolilolidine 251 was confirmed by single crystal X-ray diffraction?’ and a perspective drawing of the crystallographically determined structure is shown in Fig. 1. When an identical sequence of reactions was conducted with ketone 22b, the &benzyloxy hydrolilolidine 2Sb was formed with similar efficiency. It is important to stress that the stereoselectivity of this hydrolilolidine synthesis follows directly from the truns relationship of the vinyl and amine groups on the cyclopentane ring of precursor 24. This feature of the rearrangement is illustrated in eq 6.

24

CH20 Ii+

-Ii+ -

230;R:Me

250;

R’=H,

24o;R=H

25b

R’ = OBn,

R2=OBn R2=H

Scheme 2. Bn = CH?Ph.

Fig. I. A computer-generated

perspective drawing of the X-ray

modelof hydrolilolidine25a.

25

(6)

L. E. OVERMAKet al.

4044

The

synthesis

CONCLUSION of 9a-arylhydrolilolidines

described

in

this report provides a further illustration of the considerable utility of “directed” cationic azaCope rearrangements in organic synthesis. Of particular importance is the demonstration that the rearrangement step occurs under mild conditions with complefe

stereoselechity

and in excellent yield. The preparative I and 2 provides a quick

sequence described in Schemes entry to 9a-arylhydrolilolidines.

The application of this chemistry to total synthesis objectives in the Aspidospema alkaloid area, as well as further synthesis applications of “directed” amCope rearrangements, will be described in future publications from this laboratory.

EXPERIMEhTAL” 2 - Ethyl - 2 - (I - benzyloxy - 3 - chloropropyi) cyclopentanone (16). Titanium tetrachloride (19.1 g, 0.10mol) was slowly added at - 78” to a soln of 29.1 g (0.10 molf of 14 (R = CH,Ph; prepared by the general procedure of Reeves”) and 5OOmL CH&. A soln of 19.3 g (0.105 mol) of 13 fbp 82-83”. 20 mm; prepared from 2-ethylcyclopentanone by the general procedure of Fleming’? and 200 mL CH2CII was added dropwise ar - 78” over 1.5 hr. and the reaction was stirred for an additional 3 hr at -78”. The reaction was quenched with 5OOmL sat NaHCO, aq and the aoueous iaver was extracted with CHCI? (3 x 250 mLf. The comb&ed organic extracts were washed-with sat NaHCO, aq 1500 mLI. brine (500 mLt. dried fCaSO,I. and concentrated. The ;esul&‘oil was‘ fractionally disiilted to give a low boiling fraction (I 1.14 g) which was mainly benzyl alcohol. A second fraction (7.4Og) contained 16 plus the debenzylated product 17: b.p. 94-98” (0.085-0.095 mm). A third fraction (9.28 g) contained pure 16: b.b. 147-W” (0.06-0.08mm). The pot residue was distilled (Kugeirohr) to give an additional 2.88g of I6 and the second fraction was redistilled to nive 1.22~. of 16 for a total yield of 13.38g (45%) of 16 as a &.cous &low oil. Separation of a comparable sample of diastereomers was accomplished by flash chromatography (silica gel, 3: I hexane-CHC&) and distillation (Kugelrohr; l45-ISO”, 0.075 mm) to give the faster moving isomer: ‘H ti:MR 6 7.3k7.23 (m, Ph). 4.50 (AB q. J = 11.0 Hz. Au = 9.2 Hz, CH,Ph), 4.02 {dd, J = 9.3. 3.4 Hz, OCH), 3.69-3.63 (m, CH2CI), I.45 fq. J = 7.3 Hz, CH,CH,). 0.88 (t. J = 7.4 Hz, CH,); IR (neat) 1732, 1087, 1068,747,732,693.6.55 cm-‘; MS (CI) m/e 295 (S), 203 (7), 189 (9). 187 (32), 91 (100); and the slower moving isomer: ‘H NMR 6 7.35-7.28 tm, Ph), 4.68 (s, CH2Ph). 3.80 (dd. J = 9.5, 2.5 Hz, OCH), 3.7&3.55 (m, CH$I). 1.60 (dq. J = 7.3, I .5 Hz, CH2CHI), 0.88 (t, J = 7.4 Hz, CH,); IR (neat) 1731, 1082. 1067. 732, 692, 649cm-‘; MS (Cl) m/e 295 (S), 203 (13). 189 (6). 187 (20). 91 (100). 4 - ~enzyfoxy - 4a - ethyl - 1 - ~efhyiocfahydeo - 1H - 1 pyrindin - 7 - 01s(20)and (21). A soln of 16 (4.42 g, IS mmol) NaI (3.38 g; 22.5 mmol) and ‘l-b&none (150 ml) was heated at reflux for 21 hr. After cooling to room temp, the mixture was diluted with 600 mL HZ0 and extracted with CHCI, (3 x 250 mL). The combined organic extracts were washed with 250mL 5% Na,S,O, aa. dried (CaSO,). and concentrated to give crude 18: IR in&i) 1?29, 1O82,1067~~31,692cm~‘. A glass &her-Porter uressure bottle was charaed with this sample of 18.8.0 g (67 mmol) rof anhyd MgSO,, 20 mL (14g, 450 mmolj of anhyd m~thylamine, and 1OOmL toluene. The sealed mixture was stirred at room temp for 60 hr. and the excess amine was removed under a stream of Ar. Filtration through Celite in a funnel blanketed with Ar gave crude 19: IR (CHCI,) 1634, 1082, 1072 cm-‘. Hydroboration of this enamine sample was accomplished by a modification of the procedure of Borowitz. I6 A 1 M soln of crane-tetrahydrofuran (35 mL, Aldrich) was added dropwise over 30 min at room temp to a soln of 19 and 20mL of dry THF. This soln was kept at room temp for 24 hr. and concentrated to give a syrup. The syrup was dissolved in 60mL 95% EtOH and l.92g (48 mmol) NaOH was added, followed by the cautious dropwise addition of 5.44g (I.63 g HzOz, 48mmol) of 30% H,O,. The tesuiting mixture was heated at reflux for 3 hr, diluted with

2SOmL brine, extracted with ether (3 x 200 mL). and the combined ether extracts were extracted with I N HCL (3 x IO0 mL). The combined acidic soln was basified with solid NaOH, extracted with ether (3 x 200 mL), dried (CaSO,), and concentrated to give 3.25 g (75%) of the crude mixture of three alcohols. The three alcohols showed characteristic signals in the 250MHt ‘H NMR spectrum for their benzyioxy methi~ hydrogens at: S 3.52 (apparent t, J = 2.6 Hz); 6 3.40 (dd, J = 4.1 and 7.4 Hz), 6 3.19 (dd, J = 5.2 and 10.2 Hz). 4 - Benzyloxy - 4a - ethyl _ I - methyloctahydro - 7H - I pyrindin - 7 _ ones (22.a) and (22b). A 2.19g (7.60 mmol) sample of the crude mixture of 20 and 21 was oxidized according to the procedure of Swern. ” The resulting crude product was dissolved in 50 mL MeOH, a catalytic amount of NaOMe f - 25 mg) was added, the soin was degassed, and heated at reflux for 30 min. The reaction was then diluted with 50 mL brine, extracted with CHCI, (3 x 50mL), and the organic extracts were washed with brine and dried (CaSO,). Distillation (Kugelrohr; l50-ISS”, 0.8 mm) gave 1.7Og (78%) of an = I: 1 mixture of 22a and 22h. Separation by flash chromatography (silica gel, 100: 1 chain-MeOH) followed by dis~illa~jon ~Kugeirohr; 145-1500, 0.06 mm) gave 665 mg (31%) of 22s and 630 mg (2%) of 22b. Compound 220: ‘H NMR 6 7.37-7.25 (m. Ph), 4.49 (AB q, J = 11.8 Hz, Av = 78.5 Hz. CH,Ph), 3.36 (dd, J = 5.9, 4.1 Hz, OCH), 2.68-2.51 (m, NCH*). 2.47 (s. NCH), 2.44 (s, NCH3), 0.87 (t? J = 7.3 Hz, CH,CH,); ‘)C NMR S 217.0 (s), 138.8 (s), 128.4 cd), 127.5 (d), 74.5 (d), 73.2 (d), 70.7 (t). 48.6 (0. 45.9 (s). 43.0 (9). 32.7 ft), 24.3 it), 23.6 (t), 23.5 It), 7.6 (9); IR (neat) 1742, 1093, 733, 693cm-‘; MS (CI) m/e 289 fl9), 288 (MH’, IOO), 231 (16), 180 123): hi& resolution MS fEIf m/e 287.189 1287.189 caicd for &&
Synthesis applications of azaCope 5.48 (d, J = 1.8 Hz, = CHH), 5.01 (d, J = 1.9 Hz, = CHH), 4.51 (AB q, J = 11.4Hz, Av=41.6Hz, CH,Ph), 3.76 (dd, J =9.9, 7.0 Hz, GCH), 3.05 (s, NCH), 0.66 (1, J = 7.7 Hz, CH,CH,); “C NMR 6 154.3, 141.6, 139.2, 128.9, 128.7, 128.5, 128.1, 127.6, 127.3, 115.1,83.6,71.7,64.9,47.1,40.4,36.1,32.1,29.9,25.8,23.9,8.1; IR (CHCI,) 3331,1093, 1026,907,691 cm-‘; MS (Cl) m/e 379 (19), 378 (MH+, 100). 377 (16). 360 (13). 270 (70), 91 (16); high resolution MS (EI) m/e 377.235 (377.235 calcd for r&H,,Nt&). (9ba) - 6a - Benzyloxy - 6aa _ethyldecahydro - 9aa - phenyl9H - pyrrolo [3,2,1 - ii] quinolin - 9 - one (2%). A mixture of crude 24s (151 mg, 0.399 mmol), paraformaldehyde (30 mg; 1.0 mmol) d-Rkamphorsulfonic acid (81 mg; 0.35 mmol) and 25mL benzene was heated at reflux for 4 hr. The mixture was quenched with 5mL 1 N NaOH and extracted with CHCI, (2~25mL). The combined organic extracts were washed with brine (25 mL), dried (CaSO,), and concentrated. The residue was purified by flash chromatography (silica gel, CHCIs) to give after distillation (Kugelrohr; l85-190”, 0.04 mm) 129 mg (83%) of 2s~ as a chromatographically homogeneous heavy oil. Precipitation of this sample from pentane followed by recrystallization from pentane gave 56.2 mg clear crystals. A second recrystallization from pentane led to smaller cubes which were used for the X-ray analysis; while concentration of the mother liquid (from this crop) gave the analytical sample: m.p. 115.5-116.5”; ‘H NMR 8 7.37-7.12 (m. 2Ph). 4.49 (AB q,i = Il.8 Hz, AV = 80.3 Hz, CH*Ph), 3.37 (1. J = 2.5 Hz. OCHl. 3.16 s. NCH). 0.62 (t. J = 7.3 Hz. CH,CH>) 13C NMR 6 212.i (s), 143.4 (s), 139.2 (s), 128.7 (d), 128.5 (d), 127.7 (d), 127.6 (d), 126.7 (d), 126.5 (d), 75.7 (d), 73.2 (d), 71.0 (1). 62.9 (s). 52.0 (047.9 (I), 42.0 (s), 36.9 (I). 35.8 (t), 27.2 (t) 23.7 (t), 23.6 (0, 7.0 (9); IR (KBr) 1700, 1160, 1087, 1070, 1055, 753, 741, 691 cm-‘; MS (Cl) m/e 391 (25). 390 (MH’, 100) 298 (19). 283 (9). Calc. for CzsH3,N02: C, 80.17; H, 8.02; N, 3.60%. (Found: C, 80.40; H, 8.12; N, 3.57). (9ba) - 68 - Benzyloxy - 6aa - ethyldecahydro - 9aa - phenyl 9H - pyrrolo - 13.2.1 - ij] quinolin - 9 - one (ZSb). Using the procedure described for the preparation of 25s. an 86% yield of t5b was obtained: m.p. 99.5-100.5” ‘H NMR S 7.397.13 (m, ZPh), 4.51 (AB q. J =‘I 1.8 Hz, Av = 65.4 Hz, C&Ph), 3.46 (dd, J = 11.0. 4.7 Hz. OCH). 2.81 ts. NCH). 0.61 (1. J =7.3 Hz. CH,CH;); “C NM, 6’212.6 (si. .143.4 (4). 139.1 ‘(s). 128.7 (d), 128:4 (dj, 127.5 (d), 127.4 (d), i26.6 (d), 78.8 (d) 74.2 (d), 70.8 (t), 63.3 (s). 52.3 (0. 50.9 (0.40.8 (s). 37.0 (1). , , 36.9 It). . 28.4 It). 25.4 (0. . 25.1 (I) 7.9 (q); IR (KBr) 1705, 1180, 1093, 1073. 755. 732, 691 cm-‘; MS (CI) m/e 391 (26), 390 (MH+, 100). 283 (18). 282 (17). Calc. for Cz+,H3rN02: C, 80.17; H,8.02; N, 3.60%. (Found: C, 80.24; H, 8.06; N, 3.55). Acknowledgemen&Support from the National Institutes of Health (NS-12389) and the Cammille and Henry Dreyfus Foundation (teacher-scholar award to L.E.O.) is gratefully acknowledged. NMR and mass spectra were determined with spectrometers purchased with the assistance of NSF instrumentation grants.

REFERENCES

‘R. M. Horowitz and T. A. Geissman, 1. Am. Chem. Sot. 72, 1518 (1950). *For a recent review see: H. Heimgartner, H. -J. Hansen,; H. Schmid, Iminium Salts in Organic Chemistry (Edited by Bohme, H.,; Viehe, H. Cl.,) Part 2: 655-732. Wiley New York (1979). ‘L. E. Overman and M. Kakimoto, i Am. Chem. Sot. 101, 1310 (1979).

rearrangements

4045

‘L. E. Overman, M. Kakimoto and M. Okawara, Tetrahedron Letters 4041 (1979). ‘L. E. Overman and C. Fukaya, 1. Am. Chem. Sot. 102, 1454 (1980). 6L. E. Overman and T. Yokomatsu, 1. Org. Chem. 45, 5229 (1980). ‘L. 0. Overman and L. T. Mendelson, J. Am. Chem. Sot. in press. *For a total synthesis of dl-gephyrotoxin see: R. Fujimoto, Y. Kishi and J. F. Blount, Ibid. IQ, 7154 (1980). 9Cf D. R. Dalton, The Alkaloids. The Fundamental Chemistry Marcel Dekker, New York (1979). ItThis ring system is often called (incorrectly) hydrolulolidine in the literature. ” Hydrolilolidine 12 (R = H) would be correctly named 9a a - avl - 6a a - ethyl - 12,4,5,6&.7,8,9a,9b a -decahydro - 9H - pyrrolo [3,2,1 - ij] quinolin - 9 - one. “Hydrolilolidines with 9a-hydrogen substituents were intermediates in the original Stork and Ban syntheses of the Aspidospenna skeleton: see K. Nakanishi, T. Goto, S. Ito, S. Natori, and S. Nozoe. Natural Products Chemistry Vol 2 pp U5. Academic Press, New York (1975); Other syntheses of hydrolilolidines with 9a-hydrogen substituents include: M. E. Kuehne and C. Bayha, Tetrahedron Letter 131 I (M6); R. V. Stevens, J. M. Fitzpatrick, M. Kaplan,; R. L. Zimmerman, 1. Chem. Sot. Chem. Commun. 857 (1971) S. F. Martin, S. R. Desai, G. W. Philins. A. C. Miller. 1. Am. Chem. Sot. 102.3294 11980). ‘*Cf T Muhaiyama, ‘H. Ishihara, K. Inomata, Cheh. &f. 527 (1975). “Cf. I. Fleming and I. Paterson, Synthesis 736 (1979). “Commercially available from Aldrich. 15Prepared from acrolein and benzylalcohol by the general procedure of Reeves: H. G. Reeves, 1. Chem. Sot. 2477 (1927). I61 J Borowitz and G. J. Williams, 1. Org. Chem. 32,4157 (1%7). “A. i. Mancuso, S. -L. Huang, and D. Swern, Ibid. 43, 2480 (1978). ‘@The 250 MHz ‘H NMR spectrum showed clearly that the less stable (rans-fused ketone was initially formed from Swern oxidation” of 20. ‘9his conclusion assumes that the starting cis-relationship of the benzyloxy and ethyl groups is unaffected by the rearrangement. 2o a) Crystal data: P2,/c; a = 8.464 (I). b = 27.001 (5). c = 9.901 (I) !&and/l=74.56(l,.,P,-l.22g/ccwithz=4andCzrHs,NOz. All diffraction maxima with 205 loo” (CuKo, graphite monochromated) were recorded and 2142 (85%) of the 2513 were judged observed. Current residual is 0.063 for the observed data. (b) The library of programs used is described in 1. Am. Chem. Sot. 103, 1243-4 (1981). (c) Crystallographic Data have been deposited with the Cambridge Crystallographic data Centre, Lensfield Rd., Cambridge CB2 IEW. “M.p.‘s were determined on a Thomas Hoover apparatus and are uncorrected. ‘H NMR spectra were obtained on a Bruker WM250 spectrometer; “C NMR spectra were obtained on a Bruker WM-250 or WH-90 spectrometer. All NMR spectra were obtained in CDCI,. IR spectra were recorded on a Perkin-Elmer Model 283 spectrometer. Low resolution mass spectra (MS) were determined on a Finnigan Model 4000 GC/MS/DS by either EI (70eV) or CI (isobutane, IOOeV) modes and are reported with their relative intensities (2 10%).High resolution mass spectra were obtained with a Kratos MS-50 at the Midwest Center for Mass spectroscopy, University of Nebraska. Elemental analyses were performed by Galbraith Laboratories, Inc.. Knoxville, TN. All reactions were conducted under an Ar atmosphere. 22M S Newman, B. Dhawan, MM. Hashem, V. K. Khanna and J. M.‘Springer, 1. Org. Chem. 41, 3925. (1976).